The Medicines Company Announces Positive Top-Line Results from Day 180 Interim Analysis in Ongoing ORION-1 Phase 2 Study of Inclisiran (formerly, PCSK9si)
The Medicines Company (Nasdaq:MDCO) today announced positive top-line results from the interim analysis with Day 180 follow-up for all 501 patients enrolled in the ongoing ORION-1 Phase 2 study of inclisiran, its investigational, first-in-class PCSK9 synthesis inhibitor. In the interim analysis, inclisiran continued to demonstrate significant and durable LDL-C reduction, reaffirming the potential for a highly-differentiated, low-volume dosing regimen of two or three injections per year. Inclisiran was well tolerated and no material safety issue, including no investigational drug-related elevation of liver enzymes, neuropathy or change in renal function, was observed. Injection site reactions with inclisiran were infrequent, mild or moderate, and transient.
"Once again, we are highly encouraged by the strength and consistency of the safety and efficacy data from ORION-1, which reaffirm our confidence in the great potential of inclisiran and reinforce our decision to accelerate the development of this highly-differentiated and potentially transformational approach to treating patients with hypercholesterolemia,” said Clive Meanwell, M.D., Ph.D., Chief Executive Officer of The Medicines Company. “We continue to focus our resources on thoughtfully and aggressively advancing inclisiran into Phase 3 development to ensure that this promising new treatment option is made broadly available to the millions of at-risk, often non-adherent, patients worldwide who continue to struggle with high cholesterol using available therapies. Our initiation of the ORION-2 study and enrollment of ORION-1 patients into the ORION-3 extension study, both of which we announced today, demonstrate our strong commitment to these patients.”
The complete follow-up data for all 501 patients to Day 210 (completion of the ORION-1 study), including Day 180 efficacy data, has been submitted for presentation at the American College of Cardiology’s 66th Annual Scientific Session, to be held March 17 – 19, 2017, in Washington, DC. In order to protect the scientific integrity of the ongoing ORION-1 study, the Company does not expect to provide additional information or make further public statements regarding the results of the study until such time as the data is presented. The Medicines Company also expects to engage in discussions with regulatory authorities regarding the Company’s Phase 3 development plan for inclisiran prior to the initiation of its pivotal clinical trial, ORION-4.
Initiation of ORION-2 Study
The Medicines Company also announced today that it has initiated the ORION-2 study of inclisiran in patients with Homozygous Familial Hypercholesterolemia (HoFH). The study will examine the efficacy, safety and tolerability of inclisiran in patients with HoFH.
Initiation of ORION-3 Study
The Medicines Company also announced today that it has initiated ORION-3, a Phase 2, open-label extension study, with an active comparator (evolocumab), for patients completing the ongoing ORION-1 study. The ORION-3 study will evaluate the efficacy, safety and tolerability of long-term dosing of inclisiran and will also measure the effects of treatment, including a comparison of the effects of inclisiran and evolocumab, as well as switching from evolocumab to inclisiran, on certain clinical and patient-reported endpoints. Patients completing ORION-1 will receive inclisiran or evolocumab, based on the treatment received in ORION-1. Those patients who received inclisiran will receive inclisiran throughout the ORION-3 study. Those patients who received placebo will receive evolocumab as comparator for one year, and then switch to inclisiran for the remainder of the ORION-3 study. The estimated study period for ORION-3 is four years, or until inclisiran receives regulatory approval, whichever occurs first. Subject to discussions with regulatory authorities, the ORION-3 study will be conducted in parallel with the Phase 3 development program for inclisiran.
ORION-1 is a placebo-controlled, double-blind, randomized Phase 2 study of single or multiple subcutaneous injections of inclisiran in a total of 501 patients with atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents (e.g., diabetes and familial hypercholesterolemia), and elevated LDL-C despite maximum tolerated doses of LDL-C lowering therapies. The study compares the effect of different doses of inclisiran and evaluates the potential for an infrequent dosing regimen. The primary endpoint of the study is the percentage change in LDL-C from baseline at Day 180.
Inclisiran (formerly known as PCSK9si or ALN-PCSsc) is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9 – a genetically validated protein regulator of LDL receptor metabolism – being developed for the treatment of hypercholesterolemia.
The Medicines Company and Alnylam Pharmaceuticals are collaborating in the advancement of inclisiran per the companies' 2013 agreement. Under the terms of the agreement, Alnylam completed certain pre-clinical studies and the Phase 1 clinical study, with The Medicines Company leading and funding the development of inclisiran from Phase 2 forward, as well as potential commercialization.
About The Medicines Company
The Medicines Company is a biopharmaceutical company driven by an overriding purpose – to save lives, alleviate suffering and contribute to the economics of healthcare. The Company’s mission is to create transformational solutions to address the most pressing healthcare needs facing patients, physicians and providers in three critical therapeutic areas: serious infectious disease care, cardiovascular care and surgery and perioperative care. The Company is headquartered in Parsippany, New Jersey, with global innovation centers in California and Switzerland.
The Medicines Company Forward Looking Statements
Statements contained in this press release that are not purely historical may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates," "expects," “potential,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether clinical trials for inclisiran will advance in the clinical process on a timely basis, or at all, or succeed in achieving their specified endpoints; whether physicians, patients and other key decision makers will accept clinical trial results; whether the Company will make regulatory submissions for inclisiran on a timely basis, or at all; whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis, or at all; and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission, including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on October 27, 2016, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.